Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values
Primary Purpose
Traumatic Brain Injury
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Hypertonic saline
Mannitol
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury focused on measuring traumatic brain injury, PtiO2, Cerebral microdialysis, Osmotherapy, hypertonic saline, mannitol
Eligibility Criteria
Inclusion Criteria:
- Severe Traumatic brain injury monitored with ICP, PtiO2 and cerebral microdialysis
- And ICP> 20 mm Hg needing osmotherapy
- And approval of the next of kind
Exclusion Criteria:
- Bilateral fixed dilated pupils
- Contra-indication to multimodal neuromonitoring
- Previous CNS disease
- Contra-indication to HS (cardiac insufficiency,...)
- Natremia > 155 mmol/L or osmolarity > 320 mOsm/L
Sites / Locations
- HIA Sainte Anne
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Mannitol
Hypertonic saline
Arm Description
Outcomes
Primary Outcome Measures
Effects of HS versus mannitol on lactate/pyruvate ratio
Secondary Outcome Measures
Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose
Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy
Duration of ICP<20 mm Hg after osmotherapy
Interstitial osmolarity
Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma
Length of stay
Mortality
Glasgow outcome scale
Full Information
NCT ID
NCT01028339
First Posted
December 3, 2009
Last Updated
August 7, 2012
Sponsor
Direction Centrale du Service de Santé des Armées
1. Study Identification
Unique Protocol Identification Number
NCT01028339
Brief Title
Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values
Official Title
Mannitol Versus Hypertonic Saline to Treat Intracranial Hypertension After Severe Traumatic Brain Injury : a Comparative Study on the Effects on PtiO2 and Microdialysis Values
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Terminated
Why Stopped
No patients enrolled during 2 years
Study Start Date
July 2008 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
December 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Direction Centrale du Service de Santé des Armées
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the same effects on PtiO2 and cerebral metabolism studied through microdialysis.
Detailed Description
Mannitol is frequently used to treat intracranial hypertension after TBI. However, it can be deleterious, particularly through hyperdiuresis and risks of hypovolemia. It also needs volume compensation and induces logistical problem because of needs of high infused volume to achieve osmolar load and avoid hypotension. Finally, some recent studies tend to prove superiority of hypertonic saline versus mannitol on the prognosis of TBI. especially through modulation of inflammatory reactions mechanisms and apoptosis.
We would like to prove non inferiority of hypertonic saline versus mannitol after TBI to allow its large utilization, especially by field military doctors with specific logistical problems. For that, more than the single Intracranial Pressure, we want to study effects of HS vs mannitol not only on PtiO2 but also on cerebral microdialysis which gives informations on focal metabolism with profiles of ischemia, metabolic crisis, hyperglycolysis (possible reflect of neuronal restoration) and normality.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
traumatic brain injury, PtiO2, Cerebral microdialysis, Osmotherapy, hypertonic saline, mannitol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mannitol
Arm Type
Active Comparator
Arm Title
Hypertonic saline
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Hypertonic saline
Intervention Description
2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch
Intervention Type
Drug
Intervention Name(s)
Mannitol
Intervention Description
Mannitol
Primary Outcome Measure Information:
Title
Effects of HS versus mannitol on lactate/pyruvate ratio
Time Frame
20 min, 40 min, H1, H2, H3 and H4
Secondary Outcome Measure Information:
Title
Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose
Time Frame
20 min, 40 min, H1, H2, H3 and H4
Title
Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy
Time Frame
20 min, 40 min, H1, H2, H3 et H4
Title
Duration of ICP<20 mm Hg after osmotherapy
Time Frame
20 min, 40 min, H1, H2, H3 and H4
Title
Interstitial osmolarity
Time Frame
20 min, 40 min and H1
Title
Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma
Time Frame
Day after osmotherapy
Title
Length of stay
Time Frame
After leaving the unit
Title
Mortality
Time Frame
28th days
Title
Glasgow outcome scale
Time Frame
6th month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Severe Traumatic brain injury monitored with ICP, PtiO2 and cerebral microdialysis
And ICP> 20 mm Hg needing osmotherapy
And approval of the next of kind
Exclusion Criteria:
Bilateral fixed dilated pupils
Contra-indication to multimodal neuromonitoring
Previous CNS disease
Contra-indication to HS (cardiac insufficiency,...)
Natremia > 155 mmol/L or osmolarity > 320 mOsm/L
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry BORET, MD
Organizational Affiliation
Direction Centrale du Service de Santé des Armées
Official's Role
Principal Investigator
Facility Information:
Facility Name
HIA Sainte Anne
City
Toulon
ZIP/Postal Code
83130
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
12794404
Citation
Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, Martin C. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. 2003 Jun;31(6):1683-7. doi: 10.1097/01.CCM.0000063268.91710.DF.
Results Reference
background
PubMed Identifier
17297315
Citation
Sakowitz OW, Stover JF, Sarrafzadeh AS, Unterberg AW, Kiening KL. Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma. 2007 Feb;62(2):292-8. doi: 10.1097/01.ta.0000203560.03937.2d.
Results Reference
background
PubMed Identifier
16787640
Citation
Soustiel JF, Vlodavsky E, Zaaroor M. Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury. Brain Res. 2006 Jul 26;1101(1):136-44. doi: 10.1016/j.brainres.2006.05.045. Epub 2006 Jun 19.
Results Reference
background
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Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values
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